title: Relative contribution of Ca2+-dependent and Ca2+-independent mechanisms to the regulation of insulin secretion by glucose.
abstract: Although insulin secretion is usually regarded as a Ca2+-dependent mechanism, recent studies have suggested the existence of a Ca2+-independent pathway of regulation by glucose. Here, mouse islets were used to compare the contribution of Ca2+-dependent and -independent pathways. Glucose increased insulin release in a concentration-dependent manner both in a control medium, when it depolarizes beta cells and raises [Ca2+]i (triggering signal), and in the presence of 30 mM K+ and diazoxide, when it does not further raise [Ca2+]i but increases its efficacy on exocytosis. Both Ca2+-dependent responses were amplified by glucagon-like peptide-1+acetylcholine, and were strongly potentiated by forskolin+PMA. Under conditions of mild or stringent Ca2+ deprivation, glucose had no effect either alone or with GLP-1 and acetylcholine, and was poorly effective even during pharmacological activation of protein kinases A and C. Similar results were obtained with rat islets. It is concluded that physiological regulation of insulin release by glucose is essentially achieved through the two Ca2+-dependent pathways without significant contribution of a Ca2+-independent mechanism.
authors.affiliation: Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, UCL 55.30, Brussels, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Nenquin
authors.forename: J C
authors.initials: JC
authors.lastname: Henquin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D002118:Calcium